The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A ...is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.
We report siblings of consanguineous parents with an infantile-onset neurodegenerative disorder manifesting a predominant sensorimotor axonal neuropathy, optic atrophy and cognitive deficit. We used ...homozygosity mapping to identify an ∼12-Mbp interval identical by descent (IBD) between the affected individuals on chromosome 3q13.13-21.1 with an LOD score of 2.31. We combined family-based whole-exome and whole-genome sequencing of parents and affected siblings and, after filtering of likely non-pathogenic variants, identified a unique missense variant in syntaxin-binding protein 5-like (STXBP5L c.3127G>A, p.Val1043Ile CCDS43137.1) in the IBD interval. Considering other modes of inheritance, we also found compound heterozygous variants in FMNL3 (c.114G>C, p.Phe38Leu and c.1372T>G, p.Ile458Leu CCDS44874.1) located on chromosome 12. STXBP5L (or Tomosyn-2) is expressed in the central and peripheral nervous system and is known to inhibit neurotransmitter release through inhibition of the formation of the SNARE complexes between synaptic vesicles and the plasma membrane. FMNL3 is expressed more widely and is a formin family protein that is involved in the regulation of cell morphology and cytoskeletal organization. The STXBP5L p.Val1043Ile variant enhanced inhibition of exocytosis in comparison with wild-type (WT) STXBP5L. Furthermore, WT STXBP5L, but not variant STXBP5L, promoted axonal outgrowth in manipulated mouse primary hippocampal neurons. However, the FMNL3 p.Phe38Leu and p.Ile458Leu variants showed minimal effects in these cells. Collectively, our clinical, genetic and molecular data suggest that the IBD variant in STXBP5L is the likely cause of the disorder.
Aim: To monitor the effect of adding levetiracetam in paediatric patients with hemiplegic cerebral palsy and uncontrolled epilepsy.
Methods: A case series of eight patients with hemiplegic cerebral ...palsy whose focal seizures were not adequately controlled by their current anticonvulsants were monitored after levetiracetam was added to their medications. If there was a 50% reduction in seizure frequency, then the other anticonvulsants were discontinued. Prolonged follow‐up occurred for a minimum of 2 years.
Results: There were seven males and one female whose ages ranged from 4 years to 17 years. All had focal onset seizures, while seven also had secondarily generalised tonic clonic seizures. Levetiracetam resulted in at least a 50% reduction in seizure frequency in seven, with no change in one. Three were able to wean successfully to monotherapy and remained seizure free for over 2 years. They had a prior history of infrequent seizures, one to six per year. Those who continued to require multiple anticonvulsants had a prior history of more frequent seizures, 6–50/year. Levetiracetam was well tolerated, and none ceased this because of side effects.
Conclusion: Levetiracetam is likely to be an effective anticonvulsant in children and adolescents with hemiplegic cerebral palsy and infrequent but persistent focal seizures.
X-linked West syndrome, also called “X-linked infantile spasms” (ISSX), is characterized by early-onset generalized seizures, hypsarrhythmia, and mental retardation. Recently, we have shown that the ...majority of the X-linked families with infantile spasms carry mutations in the aristaless-related homeobox gene (
ARX), which maps to the Xp21.3-p22.1 interval, and that the clinical picture in these patients can vary from mild mental retardation to severe ISSX with additional neurological abnormalities. Here, we report a study of two severely affected female patients with apparently de novo balanced X;autosome translocations, both disrupting the serine-threonine kinase 9 (
STK9) gene, which maps distal to
ARX in the Xp22.3 region. We show that
STK9 is subject to X-inactivation in normal female somatic cells and is functionally absent in the two patients, because of preferential inactivation of the normal X. Disruption of the same gene in two unrelated patients who have identical phenotypes (consisting of early-onset severe infantile spasms, profound global developmental arrest, hypsarrhythmia, and severe mental retardation) strongly suggests that lack of functional STK9 protein causes severe ISSX and that
STK9 is a second X-chromosomal locus for this disorder.
Seizures in 3‐month‐old infant when placed on stomach Harbord, Michael; Farley, Ray; McGregor, Lesley
Journal of paediatrics and child health,
November 2018, 2018-11-00, 20181101, Letnik:
54, Številka:
11
Journal Article
Background Until a few years ago, rectal diazepam (RD) was the only option available to parents and carers managing prolonged seizures. However, its use in the community was limited due to the ...requirement for privacy, and because education staff in South Australia are not permitted to carry out invasive procedures.
Method Following a literature review, a seizure management training package was developed to enhance the implementation of a trial treatment protocol for the administration of intranasal midazolam (INM). Parents, carers and education staff were later surveyed about their experiences and perceptions.
Results Intranasal midazolam was administered to 131 people (51 children and 80 adults), with 96.9% control of seizures, and only one minor adverse event. Parents expressed a preference for INM over RD because of the shorter time it took to take effect and wear off, and the ability to administer it in public if necessary.
Conclusion Intranasal midazolam is a safe and practical alternative to rectal diazepam for managing prolonged seizures in the community.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
We report a 9‐year‐old boy with seizures induced by defecation. The episodes occurred 1–2 min after passing a bowel action and consisted of initial staring, gagging, and drooling followed by a ...secondarily generalized tonic–clonic seizure. The interictal EEGs were normal, but an ictal EEG with concurrent video monitoring demonstrated a polyspike wave discharge in the left frontotemporal region. There was no evidence of syncope, and the seizures did not occur while straining to empty his bowels or immediately on standing afterward. His magnetic resonance imaging scan was normal. This is the first reported case in which ictal EEG monitoring has demonstrated reflex seizures induced by defecation.
The anticonvulsant (AED) history for 216 children and adolescents with epilepsy was reviewed to determine the incidence and types of significant side effects (SSE) which warranted ceasing the drug ...(not due to a lack of response or a high dose). All parents of patients with epilepsy seen by the author over a 2 year period (March 1996 – March 1998) were questioned about SSE to previous AEDs, and the child’s current therapy was also monitored prospectively to determine SSE. There were 107 girls and 109 boys ranging in age from 3 months – 18 years. Eighty-three patients had been exposed to a single AED while 133 had multiple AED exposures: mean 3.6 drugs; range 2–10 drugs. They were exposed to a total of 568 AEDs with SSE occurring in 15% of drug contacts: 7% due to behavioural changes such as irritability, aggression or hyperactivity; 8% were due to other factors such as a rash, headache, gastrointestinal disturbance or drowsiness. Fifty-seven children (26%) had experienced at least one SSE with 19 (9%) having SSE to more than one AED (range 2–4). Global developmental delay or an intellectual disability (ID) were present in 67 patients, and 27 (40%) of these experienced SSE compared with 30 (20%) of the group with normal cognition. This difference was principally due to the higher incidence of behavioural SSE in the ID group 28% versus 6% for the normal cognition group. Allowing for the higher number of AEDs used in the ID group (implying that their epilepsy was more difficult to control), behavioural SSE were still significantly more likely to occur in this group, i.e. 1: 9.6 drug exposures compared with 1: 31.8 exposures for the normal cognition group (P<0.001). Monotherapy trials underestimate the true incidence of SSE in clinical practice as 26% of children had experienced at least one SSE and 9% had SSE to more than one AED. Those with ID were three times more likely to have behavioural SSE than children with normal cognition.
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